PXD050727

PXD050727 is an original dataset announced via ProteomeXchange.

Title	MCM8 interacts with DDX5 to promote R-loop resolution in primordial germ cells
Description	MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that the number of primordial germ cells (PGCs) decreased dramatically after MCM8 deficiency due to proliferation defects. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9 in PGCs, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results suggest that MCM8 interacts with R-loop-resolving factors to prevent DNA damage in PGCs, thus maintaining PGC proliferation and establishing the reproductive reserve. Our findings thus reveal a novel role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:43:25.459.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Canxin Wen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-18 08:42:24	ID requested
1	2024-05-31 06:39:17	announced
⏵ 2	2024-10-22 06:43:25	announced	2024-10-22: Updated project metadata.

10.1038/S44318-024-00134-0;

submitter keyword: primordial germ cells

MCM8

R-loop

genome stability

fertility

Canxin Wen, Yajuan Yang, Shidou Zhao
contact affiliation	Institute of Women, Children and Reproductive Health, Shandong University, 250012, China
contact email	wcx12362379@outlook.com
lab head
Canxin Wen
contact affiliation	Shandong university
contact email	wcx12362379@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050727
     1. Label: PRIDE project
     2. Name: MCM8 interacts with DDX5 to promote R-loop resolution in primordial germ cells